Objective: To evaluate clinical signs and symptoms and serum levels of interleukin-6 ( IL-6), tumor necrosis factor-α (TNF-α), matrix metalloproteinase-2 (MMP-2), and vascular endothelial growth factor (VEGF) as non-invasive methods to diagnose endometriosis. Methods: Eighty women scheduled to laparoscopy underwent blood sampling for measurement of IL-6, TNF-α, MMP-2, and VEGF. The diagnosis of endometriosis was established by laparoscopy using The American Fertility Society visual diagnosis. The presence or absence of endometriosis was correlated with clinical signs and symptoms and with serum levels of those substances. Results:The sensitivity and specificity to detect endometriosis of infertility (OR 134.3) were 78 % and 98%, dysmenorrhoea (OR 11.7) were 63 % and 88 %, and chronic pelvic pain (OR 13.0) were 28 % and 100 %. The presence of rectovaginal nodules had a sensitivity 25 % and specificity 100 %. (OR 11.3, 95 %). The sensitivity and specificity of biologic markers IL-6 (OR 2.5) were 68 % and 53%, and TNF-α (OR 28.1) were 68% and 60 %. Conclusions: History of infertility, dysmenorrhea, chronic pelvic pain, dyspareunia, cervical tendess and rectovaginal nodule are clinical signs and symptoms suggesting endometriosis. IL-6 and TNF-α appears to be best serum markers for endometriosis.